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Design and Thermodynamics Principles to Program the Cooperativity of Molecular Assemblies

Dominic Lauzon, Prof. Alexis Vallée-Bélisle

First published: 17 November 2023


Most functional nanosystems in living organisms are constructed using multimeric assemblies that provide multiple advantages over their monomeric counterparts such as cooperative or anti-cooperative responses, integration of multiple signals and self-regulation. Inspired by these natural nanosystems, chemists have been synthesizing self-assembled supramolecular systems over the last 50 years with increasing complexity with applications ranging from biosensing, drug delivery, synthetic biology, and system chemistry. Although many advances have been made concerning the design principles of novel molecular architectures and chemistries, little is still known, however, about how to program their dynamic of assembly so that they can assemble at the required concentration and with the right sensitivity. Here, we used synthetic DNA assemblies and double-mutant cycle analysis to explore the thermodynamic basis to program the cooperativity of molecular assemblies. The results presented here exemplify how programmable molecular assemblies can be efficiently built by fusing interacting domains and optimizing their compaction. They may also provide the rational basis for understanding the thermodynamic and mechanistic principles driving the evolution of multimeric biological complexes.

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